The endothelial nitric oxide synthase Glu298Asp polymorphism has been suggested to play a role in the development of hypertension, atherosclerosis and coronary artery disease. To investigate functional differences between the various genotypes with respect to basal nitric oxide (NO) production, we estimated the response to endothelial NO synthase (ecNOS) inhibition by infusion of increasing doses of N G–monomethyl-l-arginine (l-NMMA) into the brachial artery during venous occlusion plethysmography. In 41 healthy subjects forearm blood flow responses to intra-arterial infusion of increasing doses of l-NMMA (0.05, 0.1 and 0.2 mg/min per dl) and norepinephrine (10, 20 and 40 ng/min per dl) were measured. The genotype of the ecNOS Glu298Asp polymorphism was assessed. Nineteen subjects had the Glu/Glu genotype, 19 subjects had the Glu/Asp genotype and three subjects had the Asp/Asp genotype. Groups were comparable concerning demographic, hemodynamic and possible confounding factors. Subjects with the Asp allele showed a reduced response to infusion of l-NMMA as compared to subjects with the Glu/Glu genotype (ANOVA, P = 0.01). There was no significant difference in the response to infusion of the NO-independent vasoconstrictor, norepinephrine, between both groups. The ecNOS Glu298Asp polymorphism is associated with reduced basal NO production and might therefore have functional implications in the development of atherosclerosis or hypertension.

Evidence on recent time trends in age–gender differences in cardiovascular drug use is scarce. We studied time trends in age–gender-specific cardiovascular drug use for primary prevention, secondary prevention, and in-hospital treatment of coronary heart disease. The PHARMO database was used for record linkage of drug dispensing, hospitalization, and population data to identify drug use between 1998 and 2010 in 1 203 290 persons ≥25 years eligible for primary prevention, 84 621 persons hospitalized for an acute coronary syndrome (ACS), and 15 651 persons eligible for secondary prevention. The use of cardiovascular drugs increased over time in all three settings. In primary prevention, the proportion of women that used lipid-lowering drugs was lower than men between 2003 and 2010 (5.7 vs. 7.3% in 2010). The higher proportion of women that used blood pressure-lowering drugs for primary prevention, compared with men, attenuated over time (15.1 vs. 13.8% in 2010). During hospital admission for an ACS, the proportion of women that used cardiovascular drugs was lower than men. In secondary prevention (36 months after hospital discharge), drug use was lowest in young women. The proportion receiving lipid-lowering drugs declined after the age of 75 in all three settings. This age difference attenuated over time. Age differences in drug use tended to attenuate over time, whereas gender differences persisted. Areas potentially for improvement are in the hospital treatment of ACS in young women, in secondary prevention among young women and the elderly, and in the continuity of drug use in secondary prevention.